Recent work in our laboratory and in others has demonstrated that certain drugs may be attached to well-defined "carrier" molecules and still retain the ability to bind to the receptor site and effect biological activity. This synthetic strategy for the attachment of drugs to carriers is termed the "functionalized congener" approach. The "carrier" molecule may be many times larger than the parent drug; indeed there is practically no maximum size limitation for a fully potent analog. Unlike the prodrug approach or the immobilization of drugs for slow release, the "functionalized congener" approach is designed to produce analogs for which no metabolic cleavage step is necessary for activation. Moreover, the attachment of the drug to a "carrier" such as a peptide may result in the enhanced affinity at an extracellular receptor site and an improvement in the pharmacological profile of the parent drug. The extracellular adenosine receptor has a modulatory role in the nervous, circulatory, endocrine, and immunological systems. The prospect of harnessing these effects specifically for therapeutic purposes is attractive, but efforts have not met with much success in the past. The functionalized congener approach has been applied to the adenosine receptor to produce analogs of agonists and antagonists which have promise as therapeutic agents and as receptor probes. In the antagonist series new analogs which combine potency, water solubility, and A1-adenosine receptor selectivity in the same compound are now being evaluated in in vivo testing.